Low-Dose R-CHOP Yields Similar Survival Benefits Compared With Standard Dose in Elderly Patients With DLBCL

Reduced-dose rituximab (RD) combined with cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin), and prednisolone (R-CHOP) had a similar complete response (CR) rate, progression-free survival (PFS), and overall survival (OS) compared with standard-dose R-CHOP or previous dose-adjusted R-CHOP chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL).

Historically, poor-risk patients with DLBCL who are treated with standard R-CHOP do not have satisfactory survival. In addition, patients who are elderly may also have decreased hematopoietic reserve, which can alter the metabolism of many drugs. This demonstrates a need for a treatment that can provide an optimum balance between efficacy and safety.

The current phase II study included 53 patients aged ≥65 years. Ho-Jin Shin, MD, PhD, and colleagues at Pusan National University in Busan, Republic of Korea, reported that complete response and overall response rates were 64.1% and 81.1%, respectively. Three-year event-free survival (EFS) and OS rates were 45.7% ± 8.4% and 62.7% ± 8.1%, respectively.¹

In a previous study that used a similar RD-R-CHOP chemotherapy schedule, Shin et al²showed that CR was 67.1%, with an overall response rate of 89.5%, a 3-year EFS of 71.9%, and a 3-year OS rate of 83.3%. They reported that the RD-R-CHOP regimen was well tolerated and effective in elderly patients with DLBCL. The favorable survival outcome served as an incentive to conduct the current study.

In the current study, patients were followed from August 2012 to December 2014 and were enrolled in the study if they had confirmed CD20-positive DLBCL, no prior chemotherapy or radiotherapy for DLBCL, Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2, and at least 1 bidimensionally measurable lesion.

Patients had a median age of 73 years (range, 65-85), with nearly 40% of them aged ≥ 75 years or older. Half of these patients had stage III/IV disease, but less than 6% had bulky disease and 11.3% of patients had bone marrow involvement.

The RD-R-CHOP regimen consisted of rituximab at 375 mg/m², cyclophosphamide at 600 mg/m², doxorubicin at 30 mg/m², and vincristine at 1 mg on day 1 of each cycle and 40 mg of prednisolone on days 1 to 5. Patients received granulocyte colony-stimulating factor if they experienced grade 3/4 neutropenia or febrile neutropenia during any cycle. All patients received the RD-R-CHOP regimen. Cycles were repeated every 3 weeks, with a total of 6 cycles of chemotherapy. If patients did not experience CR after the first 3 cycles, they received a total of 8 cycles of chemotherapy. After every 3 cycles of chemotherapy, tumor responses were measured using PET/CT scans to confirm CR. Each patient was evaluated every 3 months for the first 2 years after treatment and every 6 months thereafter.

The median follow-up duration was 18 months (range, 1-44) and grade 3/4 neutropenia occurred in 20 patients (37.7%). Seven patients (20.7%) experienced febrile neutropenia. After 3 cycles of chemotherapy, 28 patients (52.8%) experienced CR and 15 patients (28.3%) experienced a partial response (PR). At the end of the chemotherapy cycles, final CR and PR rates were 64.1% (34/53 patients) and 17.0% (9/53 patients), respectively (TABLE 1).

Table 1. Objective disease response

RD-R-CHOP indicates rituximab added to reduced dose of cyclophosphamide, doxorubicin, vincristine, and prednisolone.

During treatment and follow-up, 16 patients died. Nine died due to disease progression, 4 died from pneumonia during chemotherapy, and 3 died from septic shock after discontinuing chemotherapy. A total of 14 patients relapsed after chemotherapy. Univariate analyses indicated that albumin level was a predictive factor for shorter EFS and OS.

Twenty-four patients (45.3%) experienced neutropenia, including 29 patients (37.7%) who experienced grade 3/4 toxicity, with 5 patients (9.4%) having grade 3/4 anemia and 2 patients (3.5%) experiencing thrombocytopenia.

The investigators noted that the current study demonstrated similar or comparable long-term survival of patients treated with previous studies of RD regimen of CHOP-like chemotherapy, dose-adjusted infusions of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab, rituximab combined with low-dose CHOP, or age-adapted R-CHOP chemotherapy (TABLE 2).

Table 2. Comparison of Elderly Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Plus Rituximab in Previous Studies

Limitations of the current study include a relatively short median follow-up (18 months) and size of the cohort, but the investigators emphasized that the follow-up period was reasonable and the number of patients was large enough to evaluate poor prognosis factors for EFS and OS of patients with DLBCL. The results suggest the need for tailored therapy based on the geriatric assessment to determine the chemotherapeutic dosage.

References:

1. Park S, Jo JC, Do YR, et al. Multicenter phase 2 study of reduced-dose CHOP chemotherapy combined with rituximab for elderly patients with diffuse large B-cell lymphoma.Clin Lymphoma Myeloma Leuk. 2018. pii: S2152-2650(18)31060-7. doi: 10.1016/j.clml.2018.1003.
2. Shin HJ, Chung JS, Song MK, Kim SK, Choe S, Cho GJ. Addition of rituximab to reduced-dose CHOP chemotherapy is feasible for elderly patients with diffuse large B-cell lymphoma.Cancer Chemother Pharmacol. 2012;69:1165-117